title: Ceftriaxone blocks the polymerization of α-synuclein and exerts neuroprotective effects in vitro.
abstract: The β-lactam antibiotic ceftriaxone was suggested as a therapeutic agent in several neurodegenerative disorders, either for its ability to counteract glutamate-mediated toxicity, as in cerebral ischemia, or for its ability to enhance the degradation of misfolded proteins, as in Alexander's disease. Recently, the efficacy of ceftriaxone in neuroprotection of dopaminergic neurons in a rat model of Parkinson's disease was documented. However, which characteristics of ceftriaxone mediate its therapeutic effects remains unclear. Since, at the molecular level, neuronal α-synuclein inclusions and pathological α-synuclein transmission play a leading role in initiation of Parkinson-like neurodegeneration, we thought of investigating, by circular dichroism spectroscopy, the capability of ceftriaxone to interact with α-synuclein. We found that ceftriaxone binds with good affinity to α-synuclein and blocks its in vitro polymerization. Considering this finding, we also documented that ceftriaxone exerts neuroprotective action in an in vitro model of Parkinson's disease. Our data, in addition to the findings on neuroprotective activity of ceftriaxone on Parkinson-like neurodegeneration in vivo, indicates ceftriaxone as a potential agent in treatment of Parkinson's disease.
authors.affiliation: Institute of Biomolecular Chemistry of CNR, Padua Unit, Padua 35131, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ruzza
authors.forename: Giuliano
authors.initials: G
authors.lastname: Siligardi
authors.forename: Rohanah
authors.initials: R
authors.lastname: Hussain
authors.forename: Anna
authors.initials: A
authors.lastname: Marchiani
authors.forename: Mehmet
authors.initials: M
authors.lastname: Islami
authors.forename: Luigi
authors.initials: L
authors.lastname: Bubacco
authors.forename: Giovanna
authors.initials: G
authors.lastname: Delogu
authors.forename: Davide
authors.initials: D
authors.lastname: Fabbri
authors.forename: Maria A
authors.initials: MA
authors.lastname: Dettori
authors.forename: Mario
authors.initials: M
authors.lastname: Sechi
authors.forename: Nicolino
authors.initials: N
authors.lastname: Pala
authors.forename: Ylenia
authors.initials: Y
authors.lastname: Spissu
authors.forename: Rossana
authors.initials: R
authors.lastname: Migheli
authors.forename: Pier A
authors.initials: PA
authors.lastname: Serra
authors.forename: GianPietro
authors.initials: G
authors.lastname: Sechi
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D002443:Ceftriaxone / Q000494:pharmacology*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D007700:Kinetics; D013058:Mass Spectrometry; D008958:Models, Molecular; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000633:toxicity; D016716:PC12 Cells; D058105:Polymerization / Q000187:drug effects*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D013997:Time Factors; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D018663:Adrenergic Agents; D018696:Neuroprotective Agents; D051844:alpha-Synuclein; D002443:Ceftriaxone; D016627:Oxidopamine